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B Delahunt

Publications and source records attributed to B Delahunt.

At least 19 recordsLinked to original sources
PubMed1999

Loss of heterozygosity at 3p14.2 in clear cell renal cell carcinoma is an early event and is highly localized to the FHIT gene locus.

The VHL tumor suppressor gene (TSG) at 3p25-26 is strongly implicated in the pathogenesis of clear cell renal cell carcinoma (cRCC). In addition, 3p14.2 and 3p21 are suspected of harboring additional TSGs in cRCC, with FHIT being a candidate TSG at 3p14.2. We examined 87 microdissected, histologically well-defined cRCCs classified according to tumor-node-metastasis (TNM) stage (stage 1, 23 cases; stage 2, 14 cases; stage 3, 24 cases; stage 4, 26 cases) and Fuhrman grade (grade 1, 24 cases; grade 2, 19 cases; grade 3, 19 cases; grade 4, 8 cases; sarcomatoid cRCC, 17 cases) for loss of heterozygosity (LOH) at 3p14.2 and 3p25-26 using a series of precisely mapped microsatellite probes. We found that LOH at 3p14.2 exceeded LOH at 3p25-26 in frequency (69% versus 48.3%; P < 0.03) and was highly localized to markers within the FHIT gene locus (D3S1300 and D3S4260), with the majority of chromosomal breakpoints also mapping to this region. In addition, 3p14.2 LOH (P < 0.03), but not 3p25-26 LOH (P = nonsignificant), was associated with lower tumor grades (grades 1-3). These findings suggest that 3p14.2 genomic deletions may be among the earliest events in cRCC pathogenesis, preceding genomic deletions at the VHL locus. FHIT, or an as yet undiscovered TSG mapping to the D3S4103-D3S4260 interval, could be the molecular target of the 3p14.2 deletions.

Acid Anhydride Hydrolases↗
PubMed1999

CTLA-4 blockade enhances the immune response induced by mycobacterial infection but does not lead to increased protection.

The murine immune response to a pulmonary mycobacterial infection is slow to develop, allowing bacterial numbers to increase in the lung for several weeks after infection. We sought to enhance the protective immune response induced during Mycobacterium bovis BCG infection by administering an antibody that blocks the interaction of CTLA-4 with its ligands, CD80 and CD86. We found that injection of anti-CTLA-4 monoclonal antibody (MAb) greatly enhanced and accelerated the immune response, as measured by increased cellularity of the draining mediastinal lymph nodes, and enhanced antigen-inducible proliferation and gamma interferon production by mediastinal lymphocytes in vitro. However, despite the apparently enhanced immune response in the mediastinal lymph node following treatment with anti-CTLA-4 MAb, there was no improvement in clearance of mycobacteria in the lungs, liver, or spleen. Examination of the primary site of infection, the lung, revealed that CTLA-4 blockade had no effect on the number or function of lymphocytes infiltrating the infected lung tissue. Taken together, these data suggest that in vivo CTLA-4 blockade enhances mycobacterial-infection-induced lymphocyte expansion and effector cell cytokine production in the draining lymph node but does not alter the number or function of lymphocytes at the primary site of infection and therefore does not lead to enhanced clearance of the infection.

Abatacept↗
PubMed1999

Infection of mice with Mycobacterium bovis-BCG induces both Th1 and Th2 immune responses in the absence of interferon-gamma signalling.

A murine pulmonary infection model using Mycobacterium bovis-BCG was used to study the development of Th1 and Th2 type responses in mice lacking a functional IFN-gamma receptor (IFN-gamma R-/-). Strikingly, the IFN-gamma R-/- mice maintained the Th1 response and developed a profound M. bovis-BCG, specific Th2 type immune response characterized by IL-5-producing CD4+ T cells, eosinophil infiltration of granulomas, and significantly elevated serum IgE levels. The increase in IL-5 production and eosinophil recruitment into the lung could be detected within the first 1-2 weeks of infection, indicating that the Th2 response was not due to greatly enhanced bacterial numbers observed later in infection. These results clearly indicate that IFN-gamma acts during M. bovis-BCG infection to suppress the development of Th2 immune responses. Furthermore, they demonstrate that IFN-gamma is not a necessary cofactor in the development of Th1 type cells secreting IFN-gamma. In conclusion, these data demonstrate that IFN-gamma plays a major role in suppressing a potentially disease-promoting Th2 immune response during mycobacterial infections.

Animals↗
PubMed1998

Cystic embryonal sarcoma of kidney: a case report.

BACKGROUND: Morphologic analysis of malignant renal tumors of childhood and adolescence has resulted in the identification of a variety of tumor types with characteristic histology and clinical behavior. The authors report a case of renal sarcoma in a 19-year-old male that differs in morphology from the various established categories of primitive renal tumors. METHODS: Sections taken from the nephrectomy specimen were stained by routine methods and by immunohistochemistry for stromal and epithelial markers, and for proliferation markers. In addition, ultrastructural studies were undertaken. RESULTS: The tumor, which the authors termed cystic embryonal sarcoma, was comprised of poorly differentiated malignant mesenchyme in a myxoid stroma. Numerous epithelial-lined cysts were present. The distribution of the cysts and proliferation kinetics of cyst-lining epithelial cells suggested that they were derived from entrapped renal tubules. The tumor showed early recurrence postoperatively and after aggressive chemotherapy. The pathologic features and clinical behavior of the tumor resemble those of 2 previously reported cases and an additional 25 cases from the files of the National Wilms' Tumor Study Pathology Center. CONCLUSIONS: The clinical and histologic features of cystic embryonal sarcoma differ from those of other renal tumors of childhood and adolescence, and the tumor appears to be a novel form of renal malignancy.

Adult↗
PubMed1998

Fine-needle aspiration cytology of metastatic clear-cell renal carcinoma presenting as a solitary mass in the head of the pancreas.

In nearly 25% of patients with primary renal-cell carcinoma, metastasis is not uncommon and usually does not give rise to difficulties in diagnosis. However, its presentation as a mass in the head of the pancreas following an elapse of several years after the initial diagnosis of renal carcinoma is not only uncommon but may be confused clinicoradiologically with a primary pancreatic adenocarcinoma. The case presented here illustrates such an example with an emphasis on the usefulness of fine-needle aspiration cytology (FNAC) in the diagnosis.

Adenocarcinoma, Clear Cell↗
PubMed1998

IL-4, IL-5 and IL-10 are not required for the control of M. bovis-BCG infection in mice.

Mycobacterial infections in mice are normally characterized by a profound Th1 cell-mediated immune response, in which T cells secrete large amounts of IFN-gamma. Recent evidence suggests that this response also includes a Th2 component. In order to investigate whether production of IL-4, IL-5, or IL-10 influenced the outcome of a Mycobacterium bovis-bacille Calmette-Guérin (BCG) infection, we intranasally infected IL-4, IL-5, and IL-10 gene-deficient and control mice and monitored the resulting immune response and bacterial clearance. IL-4, IL-5, and IL-10 deficient mice cleared the mycobacteria with the same kinetics as control mice. Furthermore, T cells of cytokine deficient and control mice produced similar levels of IFN-gamma following in vitro stimulation with purified protein derivative (PPD) from M. bovis. We conclude that the cytokines IL-4, IL-5 and IL-10 are not essential for and do not negatively influence the protective immune response against M. bovis-BCG in the lung of mice.

Administration, Intranasal↗
PubMed1998

Microvessel density as a prognostic marker for transitional cell carcinoma of the bladder.

OBJECTIVE: To investigate the prognostic significance of mean vascular density (MVD) in a variety of transitional cell carcinomas (TCC) obtained by biopsy and cystectomy, and thus determine the importance of vascular density as a prognostic indicator for vesical TCC. PATIENTS AND METHODS: Tumour vasculature was visualized using factor VIII immunohistochemistry. The MVDs of tumours from 42 cystectomy specimens were correlated with patient survival over a maximum follow-up of 156 months. The results were also compared with those obtained from initial bladder biopsy in a subset of 29 patients. RESULTS: Twenty-five patients had died over a mean follow-up of 32 months. The MVDs from cystectomy specimens ranged from 29 to 229 vessels per medium-power field (0.94 mm2) while that for biopsies before cystectomy ranged from 51 to 155 vessels. The MVD for both cystectomy and biopsy specimens showed a significant association with survival, but this was absent in a multivariate analysis that included tumour stage and grade, and there was a poor correlation between the MVD of cystectomy- and biopsy-derived tumours. CONCLUSION: The assessment of tumour vascularity appears to be of little clinical importance for vesical TCC.

Adult↗
PubMed1998

Reproducibility of new classification schemes for the pathology of ductal carcinoma in situ of the breast.

AIM: To compare the interobserver variation in the pathological classification of ductal carcinoma in situ of the breast using two recently proposed classification schemes. METHODS: 11 pathologists classified a set of 25 cases of ductal carcinoma in situ chosen to reflect a range of lesions, using the traditional architectural classification together with the modified cytonuclear grading scheme of Holland et al and the Van Nuys classification scheme. Participating pathologists received a standard tutorial, written information, and illustrative photomicrographs before their assessment of the cases. RESULTS: Interobserver agreement was poorest when using the architectural scheme (kappa = 0.44), largely owing to variations in classifying lesions with a mixed component of patterns (kappa = 0.13). Agreement was better using the modified cytonuclear grading scheme (kappa = 0.57), with most consistency achieved using the Van Nuys scheme (kappa = 0.66). Most discordant results using the later scheme were due to inconsistency in assessing the presence or absence of luminal necrosis. CONCLUSIONS: Both the new classification schemes assessed in this study were an improvement over the traditional architectural classification system for ductal carcinoma in situ, and resulted in more reproducible pathological assignment of cases. The Van Nuys classification scheme is easy to apply, even to small areas of carcinoma, resulting in acceptable interobserver agreement between reporting pathologists. Additional work will be required to arrive at a consensus definition of necrosis for cases in the non-high-grade group.

Breast Neoplasms↗
PubMed1998

Histopathologic prognostic indicators for renal cell carcinoma.

Assessment of prognostic markers for renal cell carcinoma (RCC) has produced varying and often conflicting results. There is evidence to indicate that tumor stage is significantly associated with outcome, with extrarenal tumor spread being correlated with poor patient survival. The significance of other staging categories is debated, and the predictive value of tumor size for localized tumors, and infiltration of the renal vein and inferior vena cava is less certain. Numerous studies have investigated the association of tumor grade, based on nuclear or a combination of nuclear and cytoplasmic characteristics, with patient survival for RCC. There is substantial agreement that tumors of high nuclear grade and those with sarcomatoid differentiation are associated with poor patient outcome, whereas the predictive nature of other grading categories is debated. In particular, there is growing evidence to show that in four division grading systems, the upper two grading categories have similar survivals. Of other prognostic parameters tested in various prospective and retrospective studies only assessment of tumor proliferation markers (silver-staining nucleolar organizer regions, proliferating cell nuclear antigen, and Ki-67 antigen) have shown any consistency of association with survival. Tumor angiogenesis, nuclear morphometry, tumor suppressor gene, and growth factor expression have, in some studies, been correlated with survival for patients with RCC; however, contrary findings have been reported, and there is no consensus on the prognostic significance of these parameters for RCC.

Biomarkers, Tumor↗
PubMed1997

The Heidelberg classification of renal cell tumours.

This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996. The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic to the kidneys. The proposed classification subdivides renal cell tumours into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most commonly documented genetic abnormalities. Benign tumours are subclassified into metanephric adenoma and adenofibroma, papillary renal cell adenoma, and renal oncocytoma. Malignant tumours are subclassified into common or conventional renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and renal cell carcinoma, unclassified. This classification is based on current genetic knowledge, correlates with recognizable histological findings, and is applicable to routine diagnostic practice.

Humans↗
PubMed1997

Ultrastructure of streptozotocin-induced renal tumours in mice.

Streptozotocin-induced tumours in the kidneys of experimental animals have been shown to be histologically similar to human renal cell carcinoma. We report the ultrastructural features of renal tumours induced in 15 mice by a single intravenous bolus of 2.5% streptozotocin administered in a dose of 250 mg streptozotocin/kg mouse body weight. Animals were sacrificed 232-361 days after the administration of streptozotocin. On examination both kidneys from each animal contained 1-4 dysplastic tubules and 1-3 discrete tumours per kidney. Twelve dysplastic proximal convoluted tubules showing varying degrees of epithelial atypia and nine tumours exhibiting either a papillary or solid architecture were examined. Dysplastic epithelial cells and tumours of papillary and solid type exhibited complex cell borders with well-developed junctional complexes. The majority of cells contained surface microvilli, and in some cells microvilli-lined intracytoplasmic lumina were observed. Occasional dysplastic epithelial cells and tumour cells contained double-membrane vesicles 120-200 nm in diameter. These were similar to the intracytoplasmic vesicles characteristic of human chromophobe renal cell carcinoma. Intracytoplasmic collections of glycogen granules and flocculant protein were identified in both dysplastic and neoplastic cells, and where prominent they resulted in compression of cytoplasmic organelles. Coated vesicles were commonly observed. These were free within the cytoplasm and were also seen budding from strands of rough endoplasmic reticulum. The distribution of these vesicles suggested a role in protein transport from the rough endoplasmic reticulum. It is concluded that while streptozotocin-induced renal tumours have some ultrastructural features in common with human chromophobe renal cell carcinoma, the overall ultrastructural morphology differs significantly from that described for the various histological types of human renal cell carcinoma.

Animals↗
PubMed1997

Prognostic significance of microscopic vascularity for clear cell renal cell carcinoma.

OBJECTIVE: To investigate the association between tumour vascularity and patient survival in a series of clear-cell renal cell carcinoma (RCC), which often metastasizes via the vascular route and frequently has a prominent vascular network. MATERIALS AND METHODS: Vessels were labelled in sections from 150 cases of clear cell RCC by factor VIII immunohistochemistry. The mean microvessel density (MMD), expressed as the number of vessels per 10 high-power fields (HPFs, x400, aggregate field area 1.452 mm2) and tumour microvessel area (TMA), expressed as the percentage of the total tumour area within 10 HPFs, were measured for each case. The relationship between MMD and TMA, tumour stage and grade, and patient survival over a 5-year follow-up was determined. RESULTS: Tumour MMD ranged from 1 to 238 vessels per HPF, while the TMA was 1.2-60.8%. There was a weak but significant difference for MMD between tumour grades (P < 0.01) and stages (P < 0.05). There was no significant association between TMA and either tumour stage or grade. Division of cases according to MMD < or = 40 and > 40 per HPF showed a significant difference in survival curves between both groups, with a higher MMD being associated with longer patient survival. The significant association between MMD and survival was retained for stage 3 tumours only when cases were stratified according to Robson's stage at presentation. TMA did not correlate with survival. CONCLUSIONS: The assessment of tumour vascularity is of prognostic significance for clear cell RCC. The significant inverse relationship between MMD and patient survival suggests that for tumours with a poor prognosis, decreased MMD is associated with tumour fibrosis and the development of large diameter vascular channels.

Adenocarcinoma, Clear Cell↗
PubMed1997

Polyclonal Ki-67 expression in transitional cell carcinoma of the bladder.

The proliferation kinetics of 101 cases of transitional cell carcinoma (TCC) and seven cases of transitional cell carcinoma-in-situ of the bladder were assessed following staining with polyclonal Ki-67 antibody (pKi-67). Labeling indices ranged from 49% to 60.2% with a mean value of 22.2% for all cases. A significant association between pKi-67 indices, tumor grade and tumor stage was observed, with significant differences between pKi-67 indices of Grade 1 and 3 tumors and Grade 2 and 3 tumors. Significant differences in labeling indices were also found between superficial (Ta) tumors and both musculoinvasive (T2/T3a) tumors and those infiltrating the perivesical fat (T3b). pKi-67 indices for carcinoma-in-situ were similar to those noted for Grade 1 TCC. No difference in pKi-67 index was found when tumors were classified according to the morphology of the tumor invasion front. It is concluded that pKi-67 index is a useful marker for tumor progression for vesical TCC and that this immunohistochemical stain may assist clinical assessment of the potential behaviour of tumors in individual cases.

Antigens, Neoplasm↗
PubMed1997

Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors.

Papillary renal cell carcinoma is the second most common carcinoma of the renal tubules and has been characterized genetically. Its morphologic features are incompletely characterized. It has been suggested that the presence of cytokeratin 7 is specific for papillary renal cell carcinoma. Collecting duct carcinoma might have papillary architecture, and it has been suggested that reaction with the Ulex europaeus lectin is specific for it. Sections from 105 papillary renal cell carcinomas larger than 12 mm in diameter from 100 patients were studied, and immunohistochemical reactions were performed on 91. The tumors formed two morphologic groups. Type 1 (67 tumors) consisted of papillae and tubular structures covered by small cells with pale cytoplasm and characterized by small oval nuclei with inconspicuous nucleoli, frequent glomeruloid papillae, papillary edema, foamy macrophages in papillary cores, and psammoma bodies. Type 2 (38 tumors) consisted of papillae covered by large cells with abundant eosinophilic cytoplasm and characterized by pseudostratification and large spherical nuclei with prominent nucleoli, glomeruloid papillae, psammoma bodies, edematous papillae, and foamy macrophages in papillary cores are uncommon. Type 2 tumors were larger, more common in patients younger than age 40, and more frequently Stages 3 or 4 than were Type 1 tumors. Pseudocapsules were common in both and often were infiltrated by carcinoma. Sarcomatoid foci were found in five tumors. Eleven were stage T1, 54 T2, 23 T3, and 12 T4. Reaction for cytokeratin 7 was strong or moderate in 48 of 61 Type 1 tumors, and reaction was null in 24 of 30 Type 2 tumors. No tumor reacted with U. europaeus lectin.

Adolescent↗